There is controversy regarding the degree to which HIV infection and/or highly active antiretroviral therapy (HAART) contribute to the risk for cardiovascular disease (CVD). The Multicenter AIDS Cohort Study (MACS) is a unique long-standing multi-center observational longitudinal cohort study of men who have sex with men (MSM) in four U.S. metropolitan areas, and includes both HIV-infected (HIV+) and HIV-seronegative (HIV-) men. In the MACS, the number of CVD events is relatively low;therefore, to study this question, we have conducted a subclinical CVD study including coronary artery calcium (CAC) by CT scanning and carotid intima media thickness (IMT) and plaque by ultrasound. The initial cross sectional analyses are equivocal. These tests are now being repeated in the same men to evaluate short-term (3-year) longitudinal changes in these parameters of subclinical CVD. These equivocal results suggest that further study with more sensitive and specific imaging modalities, and/or longer follow-up of people treated with HAART, are necessary to examine potential associations between HIV infection and/or HAART and CVD and to identify factors associated with subclinical and ultimately clinical CVD. Both improved imaging and longer follow-up can be accomplished by continuing and extending the CVD studies begun in the MACS. Therefore, the specific aims of this application are: 1) to determine whether there is a difference in the a) prevalence and b) progression of subclinical CVD between HIV+ and HIV- men;and 2) to determine whether metabolic, inflammatory, immunologic and anthropomorphic markers potentially associated with HAART and/or HIV infection are associated with presence and/or progression of subclinical CVD, thus identifying potential mechanisms leading to subclinical CVD in this population. To address these aims, we will obtain the following studies in HIV+ and HIV- men (1) CT angiographic imaging of the coronary arteries (CTA), a novel technology that can visualize calcified as well as non-calcified atherosclerotic plaque, (2) measures of inflammatory, immunologic, metabolic, and anthropomorphic parameters with blood assays and CT imaging and (3) longitudinal changes in CAC and carotid IMT to build on the existing data that have been obtained in the MACS CVD substudy. Since HIV disease is associated with myocardial dysfunction we will characterize the prevalence and risk factors for left ventricular systolic dysfunction. An important strength of the MACS is the inclusion of a control group of HIV- men of similar demographics and HIV risk behaviors as HIV+ men. These men have been followed longitudinally with the same MACS protocol, thus allowing a comparison to the underlying population. As the number of people treated with HAART continues to rise, the need to further refine our understanding of any potential CVD risks becomes critical. The proposed studies will lead to an increased understanding of vascular and myocardial disease in HIV infection and potential mechanisms leading to subclinical CVD which can later be used to develop effective CVD prevention strategies in this population. There is controversy regarding the degree to which HIV infection, highly active antiretroviral therapy (HAART), or immune suppression contribute to the risk of CVD. This study will use novel imaging technology to measure subclinical vascular and myocardial disease and examine mechanisms for increased risk in HIV- infected compared with HIV-seronegative men. Results can be used to target prevention strategies. (End of Abstract)